Results from panitumumab (pmab) regimen evaluation in colorectal cancer to estimate primary response to treatment (PRECEPT): Second-line treatment with pmab and FOLFIRI by tumor KRAS status

Abstract

4067^ Background: Pmab, a fully human antibody to the epidermal growth factor receptor (EGFR), is indicated as monotherapy for treatment of metastatic colorectal cancer (mCRC). Mutation status of KRAS in mCRC tumors has recently been shown to predict response to anti-EGFR antibody therapies. The effect of KRAS tumor status on the efficacy of second-line pmab + FOLFIRI was evaluated in this prospective analysis. Methods: Patients (pts) were enrolled in this phase 2, open-label, single-arm study after failure of first-line treatment with oxaliplatin-based chemotherapy + bevacizumab. Pts with unresectable, measurable disease; ECOG status 0/1; with tumor samples available for KRAS testing were eligible. Pts received pmab 6 mg/kg + FOLFIRI Q2W until disease progression or intolerability. Tumor assessments were performed at wks 8, 16, 24, 32, and Q12W thereafter. DNA extracted from fixed tumor sections was used to determine KRAS status by real-time PCR. Efficacy (objective response, progression-free survival [PFS], and overall survival [OS]) and safety were evaluated by KRAS status. Results: In an interim analysis (May 2008) of 115 pts who had received ≥ 1 dose of pmab, 109 pts had known KRAS status (59% had tumors with wild-type [WT] KRAS, 41% had mutant [MT] KRAS tumors), and 102 pts had the opportunity to have their first tumor assessment. Efficacy outcomes by KRAS status are shown ( Table ). Pmab-related AEs were reported in 93% of pts; 87 pts (76%) had ≥ grade 3 AEs (related and unrelated). Most common AEs were skin-related toxicities (86% of pts), diarrhea (72%), and nausea (53%); there was no evidence that incidence of AEs was related to KRAS status. Conclusions: In interim analyses, numerical differences in PFS and OS in favor of pts with WT KRAS were observed. Pmab had a safety profile consistent with other FOLFIRI + pmab trials. Final efficacy and safety data will be presented. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .